The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease

Abstract

Background and aims: Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD.

Methods: This single-center, prospective, cross-sectional, proof-of-concept, and observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD.

Results: Periodontal disease was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups.

Conclusions: Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative 'pro-inflammatory' microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Keywords: dysbiosis; inflammatory bowel disease; microbiota; oral hygiene; periodontal disease.

Figure 1

Trial profile.

Figure 2

Comparisons of systemic inflammation levels plus oral, diet, and alcohol total composite scores between control and disease severity in inflammatory bowel disease (IBD) participants. (a-b) active-IBD participants had significantly elevated serum C-reactive protein levels and plasma IL-6 levels compared with both healthy controls (HC) and inactive-IBD participants. (c) The total oral hygiene behavior questionnaire composite scores indicate no differences between the groups. (d) The total Mediterranean-Eating-Patterns-for-Americans scores were significantly lower in the aIBD group than in the HC and iIBD groups. Consumption of (e) ‘high’ quality Mediterranean foods and (f) ‘low’ quality Mediterranean foods were both significantly lower in aIBD participants. (g) Total alcohol consumption was not different between groups based on alcohol-use-disorders-identification-questionnaire scores. The Kruskal–Wallis test was used to assess differences across groups. Adjusted p values (q values) between group comparisons are presented using the Benjamini–Hochberg method.

Figure 3

Alterations in oral and gut microbiota composition at different sampling sites. Visualization of oral and fecal microbial community structures in (a) unstimulated saliva, (b) stimulated saliva, (c) gingiva swab, (d) tongue swab, and (e) feces between the healthy control and disease severity inflammatory bowel disease (IBD) groups. Analyses were performed using Non-Metric-Multi-Dimensional-Scaling plot-based Aitchinson distances using amplicon sequence variants counts from rarefied sequences. Symbols representing each group sample are connected to a centroid representing the mean value of each group: healthy controls (green), inactive-IBD (blue), and active-IBD (red). Refer Table 4 for corresponding Permutational Multivariate Analysis of Variance/Permutational Analysis of Multivariate Dispersions data.

Figure 4

Site-specific differential abundances of bacterial genera between healthy control and disease severity inflammatory bowel disease (IBD) groups. Mean relative abundance of microbial genera (>1%) in (a) unstimulated saliva, (b) stimulated saliva, (c) gingiva swab, and (d) tongue swab between groups. (e-o) Significantly differentially abundant genera are shown for each oral sampling site to identify taxon alterations between groups. (p) Oralization of stool microbiota, characterized by a significant increased relative abundance of Streptococcus, occurs in IBD. Bold taxa indicate a significant difference between groups assessed using Centered-Log-ratio-Kruskal–Wallis to generate p values and corrected using the Benjamini–Hochberg method (q value).